Dietary linoleate effect upon prostaglandin and thromboxane synthesis

PROSTAGLANDINS

DIETARY LINOLEATE EFFECT UPON PROSTAGLANDIN AND THROMBOKANE Melvin M. Mathias, Karen Fiiie, Barbara Lipiniic'i, SYNTHESIS, a-'Jacqueline DuPont, Department of Food Science and Nutrition, 80523. Colorado State University, Fort Collins Colorado ABSTRACT Composition of dietary fat may be a major biomedical mode of altering the profile and amount of prostaglandins (PG) and thromboxanes (TB) produced by tissues. Alterations in the composition of precursor fatty acid pools should be reflected in the amount of PG and TB synthesized ex vivo and the ratio of 1, 2, and 3 series of PG. Rats were fed 8 levels of dietary linoleate Whole varying from O-30% of total calorie intake for l-6 months. blood and adipocytes were incubated at 37O for 10 or 60 minutes, respectively, and PG production was inhibited by adding aspirin. PGF2b , E , El and TB2-like substances were measured by RIA. Platglet production of PG and TB as reflected by clotting of whole blood showed a biphasic response with respect to the amount of dietary linoleate. There was a marked increase in PGF2&, El and TB2 levels with linoleate equivalent to O-l% calories, a decrease with 5%, and then F &, and El linearly increased with 30%. PGE with all linoleate leve ? s increased 2-fold. TB continued to 2 ecrease with 20% linoleate, then increased 3 fol 5 between 20 and 30%. A statistically significant linear rise in PGEl, E2 and F2G production (TB not determined) by adipocytes incubated in the presence of norepinephrine was observed between 1% and 20% linoleate calories. These results indicate the complex relationship between dietary fat and PG and TB synthesis. (Supported in part by NIH grant HL#-18239 and USDA, CSRS Special Project Grant.) THE HYPERALGESIC EFFECTS Q.__SROSTAGI&NNINS I2 and E?. Sergio H. Ferreira, Meire Nakamura and Maria Salete de Abreu Castro, Dept. of Pharmacology, Faculty de Medicine de Ribeirao Preto, Brazil. ABSTRACT The hyperalgesic effects of PG12 (prostacyclin) and PGE2 were tested in rats and dogs. A modification of the Randall-Selitto test (Arch. Int. Pharmacodyn. 111, 409, 1957) , in which a constant pressure of 20 mmHg is applied to the paw, was used for rats. The intensity of hyperalgesia was evaluated by the difference between the response time before and after the injection of prostaglandin as indicated by an avoidance movement. The intensity of hyperalgesia in the dog was evaluated by the degree of incapacitation caused by the intraarticular injection of prostaglandins (Resent le et --* al J. Pharm. Pharmacol. 2, 149, 1972). A 5 point scale was used: O=no effect; l=mild limping: 2=severe limping: 3=dog stands on four legs but walks on 3 legs; 4=dog stands and walks without the affected leg. Indomethacin (2 mg/kg/IP in rats: 2 mg/kg/IV in dogs) was given to minimize endogenous prostaglandin synthesis. A low dose (lng) of PGI2 injected into the rat paw, caused an immediate maximal hyperalgesic effect which subsided within one hour. With higher doses (20-100 ng) the effect lasted 3-4 hours. Successive injections of 0.5 ng of PGI2 caused a long-lasting effect. The

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APRIL

1978 VOL. 15 NO. 4